The objective of this research is to continue to investigate membrane mechanisms that underly the myotonic reaction, i.e., abnormal, prolonged, repetitive discharge of action potentials and abnormal contractions of skeletal muscle fibers. Electrophysiological and pharmacological methods will be used to study skeletal muscle responses in the myotonic goat and other naturally myotonic species and in normal muscle of various species after inducing myotonia by chemical agents, ionic changes or other treatments. The mechanisms of drugs or physiological conditions that antagonize myotonia or induce the condition will be investigated. The basic electrophysiological methods to be used include the Hille-Campbell and three-electrode voltage clamps, and analysis of fiber cable properties and excitability with microelectrodes. Membrane potential probe dyes will be used in optical studies to determine the function of the transverse tubules and sarcoplasmic reticulum in myotonic fibers. The ultimate goal is to define the membrane abnormalities of myotonic fibers in terms of specific changes in the properties of ionic channels and their gating mechanisms, their voltage-time dependency and molecular alteration.